Kupffer cell-mediated lymphocyte apoptosis. A PGE2-dependent mechanism of portal venous transfusion-induced immunosuppression?

Richard V Perez, Jeremy Johnson, James D. Winkler, Steven Rudich, Lynn Carter, Steven Katznelson, J. Bruce German

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background. Kupffer cells, after exposure to alloantigen via the portal vein, mediate an immunosuppressive effect involving enhanced production of PGE2. We hypothesize that up-regulation of Kupffer cell CoA-independent transacylase (CoA-IT) by portal venous transfusion (PVT) is a possible mechanism of increased PGE2 production. Additionally, enhanced lymphocyte apoptosis, a process known to be macrophage dependent and facilitated by PGE2, is postulated as a possible mechanism of PVT-induced, Kupffer cell- mediated immunosuppression. Methods. Lewis rat Kupffer cells were isolated after portal venous infusion with 1 ml of Wistar-Firth blood (PVT) or saline (PV sal). Kupffer cell PGE2 production and CoA-IT activity was assessed. Lymphocyte apoptosis after exposure to PVT or PV saltreared Kupffer cells was also assessed by flow cytometry. Results. PVT-treated Kupffer cells produced significantly more PGE2 and had increased CoA-IT activity when compared to PV sal-treated Kupffer cells. Treatment of Kupffer cells with a selective inhibitor of CoA-IT significantly decreased PVT-induced Kupffer cell PGE2 production. Increased lymphocyte apoptosis was observed after coculture with PVT-treated Kupffer cells compared to PV sal-treated cells. Conclusions. PVT increases Kupffer cell PGE2 production via increased CoA-IT activity and induces Kupffer cell-mediated lymphocyte apoptosis. Lymphocyte apoptosis facilitated by Kupffer cells within the hepatic sinusoid may be an important mechanism of PTV-induced immunosuppression in organ transplantation.

Original languageEnglish (US)
Pages (from-to)37-41
Number of pages5
JournalJournal of Surgical Research
Volume78
Issue number1
DOIs
StatePublished - Jul 15 1998

Keywords

  • Apoptosis
  • CoA-independent transaycylase
  • Kupffer cells

ASJC Scopus subject areas

  • Surgery

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